DESCRIPTION: Most knowledge of coronary vascular biology is derived from animal studies. However, marked variability among species makes it difficult to extrapolate this data to the clinical arena especially, with respect to disease. Studies of coronary reactivity in humans have principally been performed in vivo, where confounding influences such as extravascular compressive forces, humoral, and neural responses cannot be controlled. Most in vitro studies which can exclude these effects have examined large epicardial conduit arteries. Little is known about direct coronary microvascular responses to physiological stimuli in humans. This is important because coronary flow is regulated at the arteriolar level. The central focus of this proposal is to utilize in vitro techniques to directly examine the mechanisms underlying myogenic vasoconstriction in human coronary arterioles obtained at the time of cardiopulmonary bypass. Myogenic constriction will be produced by changing intraluminal pressure at zero flow. Both active myogenic constriction and spontaneous myogenic tone will be evaluated. Morphologic analysis of the coronary arterioles will also be conducted to identify anatomic changes which correlate with altered vascular reactivity. The investigators will examine possible mechanisms of spontaneous as well as actively developed myogenic tone in normal coronary arterioles, focusing on the role of protein kinase C (PKC), the endothelium and calcium activated potassium channels. An additional goal of these studies is to provide an increased understanding of the mechanisms of altered human coronary myogenic reactivity in hypertension. The modulatory effect of hypertension on myogenic vasoconstriction will also be examined. Preliminary data suggest that myogenic constriction is enhanced in isolated coronary arterioles from patients with hypertension. The mechanism of this enhanced constriction will be studied in separate protocols. Independent data suggest that PKC is elevated in hypertension, and that PKC is responsible for myogenic constriction in some tissues. The investigators will examine the hypothesis that increased activity of PKC is responsible for the enhanced myogenic constriction in hypertension. Both tissue activity of PKC as well as the effects of inhibiting PKC in vessels from hypertensive patients will be compared to responses in normotensive controls. The investigators will also examine the role of increased production of endothelium derived vasoconstrictor prostanoids or reduced activity of endothelium derived nitric oxide in contributing to the enhanced myogenic constriction in hypertension.